Author’s Reply to De Ponti et al.: “Pharmacokinetics in Patients with Chronic Liver Disease and Hepatic Safety of Incretin-Based Therapies for the Management of Type 2 Diabetes Mellitus”

Excerpt

In our review about the use of incretin-based therapies in patients with chronic liver disease, the overall liver safety of dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) was considered reassuring [1]. This statement was first challenged for alogliptin in a Letter to the Editor, which emphasized the warning by the US Food and Drug Administration (FDA) concerning a possible liver toxicity for alogliptin [2]. In our response, we more specifically analyzed all of the available data regarding this DPP-4 inhibitor and concluded that the risk of liver toxicity for alogliptin is, if present, very low [3]. In a second Letter to the Editor, other researchers agreed with our conclusion for alogliptin, but pointed out an increased risk of drug-induced liver injury (DILI) with three other DPP-4 inhibitors: saxagliptin, sitagliptin, and vildagliptin [4]. Their conclusions were based upon an analysis of the publicly available FDA Adverse Event Reporting System (FAERS). Adverse event reports of overall liver injury (OLI; including acute and chronic hepatic injuries) and acute liver injury (ALI; a subcategory including only acute severe hepatic injuries) were extracted and a disproportionality approach was performed by calculating the reporting odds ratio (ROR) [4]. However, this strategy may be challenged from a methodological point of view. Furthermore, some additional information may be available for the three DPP-4 inhibitors (sitagliptin, saxagliptin, and vildagliptin) that showed a significant increase in OLI according to the analysis by Raschi and colleagues [4]. …